10-79612325-A-G

Variant names:

• chr10-79612325-A-G
• rs1136451
• NM_005411.5:c.186A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005411.5(SFTPA1):​c.186A>G​(p.Pro62Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,446 control chromosomes in the GnomAD database, including 24,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2661 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21977 hom.)
• Consequence: SFTPA1 NM_005411.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.93

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 10-79612325-A-G is Benign according to our data. Variant chr10-79612325-A-G is described in ClinVar as [Benign]. Clinvar id is 165197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 4 of 6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 4 of 6	1	NM_005411.5	ENSP00000381633.3
SFTPA1	ENST00000419470.6	c.231A>G	p.Pro77Pro	synonymous_variant	Exon 4 of 6	1		ENSP00000397082.2
SFTPA1	ENST00000428376.6	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 3 of 5	1		ENSP00000411102.2
SFTPA1	ENST00000429958.5	c.186A>G	p.Pro62Pro	synonymous_variant	Exon 3 of 5	1		ENSP00000395527.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27012 AN: 151896 Hom.: 2651 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.206 AC: 51721 AN: 251438 Hom.: 6067 AF XY: 0.203 AC XY: 27584 AN XY: 135892

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.270

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.167 AC: 244707 AN: 1461434 Hom.: 21977 Cov.: 35 AF XY: 0.169 AC XY: 123216 AN XY: 727020

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.178 AC: 27062 AN: 152012 Hom.: 2661 Cov.: 32 AF XY: 0.183 AC XY: 13619 AN XY: 74314

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.218

Alfa AF: 0.143 Hom.: 740

Bravo AF: 0.187

Asia WGS AF: 0.289 AC: 1003 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.165

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Benign based on MAF in ESP (16.7% in AA; 15.82% in EA) -

SFTPA1-related disorder Benign:1

Apr 22, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.43
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1136451; hg19: chr10-81372081; COSMIC: COSV64866675; COSMIC: COSV64866675;